CD4+ T cells are thought to play important roles in many, if not all, autoimmune diseases including illnesses such as lupus erythematosus (LE). For years it has been recognized that associations exist between a lupus patient's B cell-derived autoantibody repertoire and the clinical manifestations of his or her disease. For example, the presence of Ro/SS-A autoantibody correlates with SCLE while the presence of Sm autoantibody correlates systemic LE. Now, evidence is beginning to accumulate to associate the amplification of T-cell clones expressing sets of T cell receptors with limited and specific repertoires with autoimmune processes such as diabetes mellitus. We hope to apply a similar approach to the investigation of LE skin disease. We propose here to challenge peripheral blood T cells from patients with LE skin lesions with synthetic combinatorial peptide libraries to determine if these patients have expanded numbers of T cells bearing T cell receptors that react with discreet epitopes. If we are successful, we will then compare the precursor frequency of peptide-specific T cells in peripheral blood- and skin lesion-derived T cell populations. The results of these studies could be useful in identifying potentially pathogenetic environmental or infectious agents that might trigger these diseases through molecular mimicry and could be of value in the design of immunotherapeutic strategies for tolerance/anergy induction.